Suppression of leukocyte-enhanced cold ischemia/reperfusion injury of liver endothelium with the benzoquinone antioxidant idebenone.
OBJECTIVE
Despite the large body of evidence for a major role of neutrophils and oxidant stress, the exact pathogenesis of the early ischemia/reperfusion injury after cold preservation of the liver is not well understood. The potential benefit of an antioxidant on metabolic liver function during reperfusion has been demonstrated in several studies.


METHODS
We describe a cold storage/reperfusion damage model with isolated perfused pig livers, where the effects of neutrophils and idebenone, a recently developed benzoquinone antioxidant were studied. The integrity of sinusoidal endothelial cells (SEC) was estimated by hyaluronic acid concentration in perfusate and the expression of endothelial constitutive nitric oxide synthase (ecNOS) after reperfusion and compared to lipid peroxidation and antioxidant content.


RESULTS
Hyaluronic acid displayed the highest levels and ecNOS mRNA was most depressed in livers reperfused with neutrophils after 20 h cold storage; this was accompanied by an increase in lipid peroxidation (TBARS) and a breakdown of endogenous lipophilic antioxidants (alpha-tocopherol and coenzyme Q-10). These effects were attenuated, when neutrophils were excluded from reperfusion and almost completely abolished by the addition of 200 mumol/L idebenone.


CONCLUSIONS
These data suggest that a leukocyte-mediated damage based on reactive oxygen species markedly contributes to the reperfusion injury of SEC after cold preservation of the liver. Therefore, the presence of effective antioxidants in the early reperfusion phase may be beneficial for liver graft integrity.
Schütz
E
E
Abteilung Klinische Chemie, Georg-August-Universität, Göttingen, Germany. eschuetz@med.uni-goettingen.de
Wieland
E
E
Hensel
A
A
Niedmann
P D
PD
Dreiss
A
A
Armstrong
V W
VW
Schuff-Werner
P
P
Oellerich
M
M
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D016227:Benzoquinones / Q000627:therapeutic use*; D003080:Cold Temperature; D003864:Depression, Chemical; D004727:Endothelium / Q000166:cytology / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy*; D013552:Swine; D014451:Ubiquinone / Q000031:analogs & derivatives
D000975:Antioxidants; D016227:Benzoquinones; D014451:Ubiquinone; C036619:idebenone